Mild traumatic brain injury (mTBI), commonly called concussion, has an annual incidence estimated as 130.8 per 100,000 in the United States. The economic impact of concussion is substantial, with annual U.S. estimates reaching $3 billion, and is increasing due to more sensitive diagnosis and increased awareness. Available data indicate that the total costs for mTBI, or concussion, are high, and that the indirect costs, such as for sick leave, early retirement and loss of productivity, are the main expense.
Stroke is the fourth leading cause of death in the United States and affects 6.8 million Americans (overall prevalence 2007-2010 was 2.8%). Almost 800,000 new strokes occur each year (approximately 23% are recurrent strokes). In 2009, strokes cost the U.S. economy $38.6 billion and the mean lifetime cost of ischemic stroke is $140,048. Traumatic brain injury, intracerebral hemorrhage, and subarachnoid hemorrhage have similar if not greater prevalence and impact statistics.
A review of CSD is helpful, as the concussion and neurological injury detection systems and methods described below is based on the properties and characteristics of CSD. CSDs and their initiation by mechanical stimulation of the brain surface were first reported in 1944, but were considered an experimental curiosity until their association with acute neurological injury and their identification as the phenomenology behind migraine auras. CSDs and their pathological correlate in ischemic brain regions, peri-infarct depolarizations (PIDs), are important phenomena related to stroke and other brain pathologies. Currently, CSDs and their neurophysiological and other properties are not detectable from the surface of the scalp by existing commercial methods and devices.
CSD is a cellular depolarization wave in cerebral gray matter involving both neurons and glia with a dimensional extent of from about 3 mm to about 6 mm, which is characterized by the depression of evoked and spontaneous electroencephalography (EEG) activity from the brain spreading at a rate of 1 to 9 mm/min across the cortical surface. The spontaneous EEG remains markedly depressed for ½ to 1 min, and then returns to normal within the following 5 to 10 min, whereas the evoked synaptic activity usually takes longer to recover (i.e., 15 to 30 min). CSD is characterized by a complete loss of neuronal activity, which can last for minutes, before complete recovery. Simultaneously, the local tissue potential (the DC potential) swings negative with amplitudes of 15 to 30 mV for 1 min or more. At the surface of the scalp, this DC potential is reduced to approximately 300 μV. The EEG depression coincides with and is caused by a dramatic failure of brain ionic homeostasis and near equalization of extra-, intra-, and total brain ionic concentrations: most notably, extracellular concentration of potassium, i.e., [K+]ex increases from a normal of 3 mM to 30-60 mM. In summary, CSDs can be characterized as about 5 mm regions of cellular depolarization with high, approximately 60 mM [K+]ex, which travel at about 3 mm/min across the brain cortex with a DC potential of approximately −20 mV.
CSDs can be initiated experimentally by cortical pin-prick, electrical stimulation, cortical application of K+, or mechanical force to the cortex. Stroke PIDs, the pathological correlate of CSDs, occur in three temporal windows: 1) initial depolarization, which is fundamentally different than subsequent PIDs; 2) an acute stage of stroke (<6 h); and 3) a delayed late phase starting at 6-8 to 24 plus hours. A concussive CSD has similarities to the initial PID in ischemic stroke.
For many years, it was believed that CSD was an artifact produced in animal experiments and without significance for human neurological conditions, but its association with migraine aura and acute neurological injury has tempered this reservation.
CSD, with its properties of depressed voltage and velocity, occurs in concussion and migraine aura without morphological brain tissue damage. CSD also occurs in acute neurological injury, including ischemic stroke, severe traumatic brain injury, intracerebral hemorrhage, and sub-arachnoid hemorrhage, where it is strongly associated with the expansion of morphologically observed brain damage.
Current techniques to observe CSDs in humans require exposure of the brain surface and the placement of electrode strips, an invasive procedure termed electrocorticography (ECoG). For example, Hartings et al. (Ann. Neurol., 2014, 76:681) disclose first identifying depolarizations in ECoG recordings, then examining scalp EEG correlates. Drenckhahn et al. (Brain, 2012, 135:853) disclose observing limited regions of depressed voltage with scalp EEG associated with underlying CSDs identified with ECoG, but not the detection of a spread of slow potential change or AC-EEG depression of spontaneous activity between different scalp electrodes. Ayaz et al. (Am. J. Emerg. Med., 2015, 33:493) disclose a device that uses discriminative analysis of multiple quantitative EEG parameters from a five electrode forehead electrode array, assesses the effects of concussion on generalized neurotransmission abnormalities that are not specific to concussion, but is not sensitive to the characteristics of CSD. Nowhere in the prior art, therefore, are there disclosures to fully detect propagating CSDs noninvasively from the surface of the scalp.
The detection and diagnosis of concussion has been problematic for several reasons. Most of the acute methods, implemented soon after a concussion, are based on psychometric testing, balance assessment, or subtle eye movements. None of these methods is able to directly detect or quantify the neurological basis of concussion, and instead are performed to detect secondary indicators that can be ambiguous and inconsistent in nature. Imaging via MRI, CT, PET, ultrasound, or near-infrared spectroscopy also is not compatible with observing CSD in the setting of concussion.
There is intense interest and need for systems and methods to detect and evaluate acute sports or injury-related concussions. Post-concussion detection schemes, which are starkly distinguishable from the present invention, include ImPACT, a psychometric test that compares a pre-athletic measurement with a measurement on the sidelines for post-concussion evaluation. Although it has become the de facto standard, it is also acknowledged to be imprecise and ineffectual.
None of the prior methods or devices utilizes CSD as an indicator of concussion, which is described in more detail in the embodiments of the present invention described below.